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. 1998;17(1):191–207. doi: 10.1007/BF02786444

Rational approaches to immune regulation

Yvonne Paterson 1,✉
PMCID: PMC7090784  PMID: 9479581

Abstract

Our studies are mainly focused on developing strategies of immune regulation. In the case of infectious and neoplastic disease, our approach is to upregulate cell-mediated immunity to viral of tumor antigens using an intracellular bacterium as a vector for targeting these antigens to the major histocompatibility complex (MHC) class I and class II pathways of antigen processing, in addition to exploiting the adjuvant properties of the vector to stimulate innate immunity. In the area of autoimmunity, we are attempting to downregulate the immune response by specific immune intervention directed against autoreactive T cells. In these studies we use murine models for multiple sclerosis. Our approach is to use both rationally designed T cell receptor (TCR) peptide analogs and recombinant viral vectors that express TCR components to regulate the disease.

Key words: Antigen processing, Cell-mediated immunity, EAE, Listeria monocytogenes, Tumor immunotherapy, Vaccinia

References

  • 1.Sabin A: Presidential Address to the Infectious Disease Society of America, 1983.
  • 2.Schafer R, Portnoy DA, Brassell SA, Paterson Y. Induction of a cellular immune response to a foreign antigen by a recombinantListeria monocytogenes vaccine. J Immunol. 1992;149:53–59. [PubMed] [Google Scholar]
  • 3.Kaufmann SHE. Immunity to intracellular bacteria. Annu Rev Immunol. 1993;11:129–163. doi: 10.1146/annurev.iy.11.040193.001021. [DOI] [PubMed] [Google Scholar]
  • 4.Falkow S, Isberg RR, Portnoy DA. The interaction of bacteria with mammalian cells. Annu Rev Cell Biol. 1992;8:333–363. doi: 10.1146/annurev.cb.08.110192.002001. [DOI] [PubMed] [Google Scholar]
  • 5.Tilney LG, Portnoy DA. Actin filaments and the growth, movement, and spread of the intracellular bacterial parasite,Listeria monocyto- genes. J Cell Biol. 1989;109:1597–1608. doi: 10.1083/jcb.109.4.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6.Portnoy DA, Schreiber RD, Connelly P, Tilney LG. Gamma interferon limits access of Listeria monocytogenes to the macrophage cytoplasm. J Exp Med. 1989;170:2141–2146. doi: 10.1084/jem.170.6.2141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Czuprynski CJ, Brown JF. Dual regulation of anti-bacterial resistance and inflammatory neutrophil and macrophage accumulation by L3T4+ and Lyt 2+Listeria immune T cells. Immunology. 1987;60:287–293. [PMC free article] [PubMed] [Google Scholar]
  • 8.Mielke ME, Ehlers S, Hahn H. Tcell subsets in delayed-type hypersensitivity, protection and granuloma formation in primary and secondaryListeria infection in mice: Superior role of Lyt-2+cells in acquired immunity. Infect Immun. 1988;56:1920–1925. doi: 10.1128/iai.56.8.1920-1925.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Brunt LM, Portnoy DA, Unanue ER. Presentation ofListeria monocytogenes to CD8+ T-cells requires secretion of hemolysin and intracellular bacterial growth. J Immunol. 1990;145:3540–3546. [PubMed] [Google Scholar]
  • 10.Berche P, Gaillard J, Sansonetti PJ. Intracellular growthof Listeria monocytogenes as a prerequisite for in vivo induction of T-cellmediated immunity. J Immunol. 1987;138:2266–2271. [PubMed] [Google Scholar]
  • 11.Ikonomidis G, Paterson Y. RecombinantListeria monocytogenes cancer vaccine. Curr Opin Immunol. 1996;8:664–669. doi: 10.1016/S0952-7915(96)80083-5. [DOI] [PubMed] [Google Scholar]
  • 12.Scott P, Kaufmann SHE. The role of T-cell subsets and cytokines in the regulation of infection. Immunol Today. 1991;12:346–348. doi: 10.1016/0167-5699(91)90063-Y. [DOI] [PubMed] [Google Scholar]
  • 13.Boon T, Cerottini J-C, Van den Eynde B, van den Bruggen P. Tumour antigens recognized by T lymphocytes. Ann Rev Immunol. 1994;12:337–365. doi: 10.1146/annurev.iy.12.040194.002005. [DOI] [PubMed] [Google Scholar]
  • 14.Pardoll DM. Cancer vaccines. Trends Pharmaco Sci. 1993;14:202–208. doi: 10.1016/0165-6147(93)90209-3. [DOI] [PubMed] [Google Scholar]
  • 15.Pardoll DM. A new look for the 1990s. Nature. 1994;369:357–358. doi: 10.1038/369357a0. [DOI] [PubMed] [Google Scholar]
  • 16.Pan Z-K, Ikonomidis G, Lazenby A, Pardoll D, Paterson Y. A recombinantListeria monocytogenes vaccine expressing a model tumour antigen protects mice against lethal tumour challenge and causes regression of established tumours. Nature Med. 1995;l:471–477. doi: 10.1038/nm0595-471. [DOI] [PubMed] [Google Scholar]
  • 17.Pan Z-K, Ikonomidis G, Pardoll D, Paterson Y. Regression of established tumors in mice mediated by the oral administration of a recombinantListeria monocytogenes vaccine. Cancer Res. 1995;55:4776–4779. [PubMed] [Google Scholar]
  • 18.Ikonomidis G, Paterson Y, Kos F, Portnoy D. Delivery of a viral antigen to the class I processing and presentation pathway byL monocytogenes. J Exp Med. 1994;180:2209–2218. doi: 10.1084/jem.180.6.2209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Asher AL, Mule JJ, Kasid A, Restifo NP, Salo JC, Reichert CM, et al. Murine tumor cells transduced with the gene for tumor necrosis factor-α. J Immunol. 1991;146:3227–3234. [PMC free article] [PubMed] [Google Scholar]
  • 20.Blankenstein T, Qin Z, Ueberla K, Mueller W, Rosen H, Volk HD, et al. Tumor suppression after tumor cell-targeted tumor necrosis factor gene transfer. J Exp Med. 1991;173:1042–1052. doi: 10.1084/jem.173.5.1047. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Porgador A, Tzehova E, Katz A, Vadai E, Revel M, Feldman M, et al. Interleukin 6 gene transfection into Lewis lung carcinoma tumor cells suppresses the malignant phenotype and confers immunotherapeutic competence against parental metastatic cells. Cancer Res. 1992;52:3679–3686. [PubMed] [Google Scholar]
  • 22.Baskar S, Ostrand-Rosenberg S, Nabavi N, Nadler LM, Freeman GJ, Glimcher LH. Constitutive expression of B7 restores the immunogenicity of tumour cells expressing truncated MHC class II molecules. Proc Natl Acad Sci USA. 1993;90:5687–5690. doi: 10.1073/pnas.90.12.5687. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Guo Y, Wu M, Chen H, Wang X, Liu G, Li G, et al. Effective tumor vaccine generated by fusion of hepatoma cells with activated B cells. Science. 1994;263:518–520. doi: 10.1126/science.7507262. [DOI] [PubMed] [Google Scholar]
  • 24.Huang AYC, Gulden PH, Woods AS, Thomas MC, Tong CD, Wang W, et al. The immunodominant major histocompatibility complex class I-restricted antigen of a murine colon tumor derives from an endogenous retroviral gene product. Proc Natl Acad Sci USA. 1996;93:9730–9735. doi: 10.1073/pnas.93.18.9730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Terao M, Tabe L, Garattini E, Sartori D, Studer M, Mintz B. Isolation and characterization of variant cDNAs encoding mouse tyrosinase. Biochem Biophys Res Commun. 1989;159:848–853. doi: 10.1016/0006-291X(89)90072-7. [DOI] [PubMed] [Google Scholar]
  • 26.Hara I, Takechi Y, Houghton AN. Implicating a role for immune recognition of self in tumor rejection: passive immunization against the brown locus protein. J Exp Med. 1995;182:1609–1614. doi: 10.1084/jem.182.5.1609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Tindle RW. Human papilloma virus vaccines for cervical cancer. Cur Opin Immunol. 1996;8:643–650. doi: 10.1016/S0952-7915(96)80080-X. [DOI] [PubMed] [Google Scholar]
  • 28.Ada GL. The immunological principles of vaccination. Lancet. 1990;335:523–526. doi: 10.1016/0140-6736(90)90748-T. [DOI] [PubMed] [Google Scholar]
  • 29.Yap KL, Ada GL, McKenzie IFC. Transfer of cytotoxic T lymphocytes protect mice inoculated with influenza virus. Nature. 1978;273:238–240. doi: 10.1038/273238a0. [DOI] [PubMed] [Google Scholar]
  • 30.Plata F, Autran B, Pedroza-Martins L, Wain-Hobson A, Raphael M, Mayau C, et al. AIDS virus specific cytoxic T lymphocytes in lung disorders. Nature. 1987;328:348–351. doi: 10.1038/328348a0. [DOI] [PubMed] [Google Scholar]
  • 31.Walker CM, Moody DJ, Sittes DP, Levy JA. CD8+ lymphocytes can control HIV infection in vitro by supressing virus replication. Science. 1986;234:1563–1566. doi: 10.1126/science.2431484. [DOI] [PubMed] [Google Scholar]
  • 32.Walker BD, Chakrabarti B, Moss B, Paridis TJ, Flynn TJ, Durno AG, et al. HIV-specific cytotoxic Tlymphocytes in seropositive individuals. Nature. 1987;328:345–348. doi: 10.1038/328345a0. [DOI] [PubMed] [Google Scholar]
  • 33.Nixon DF, McMichael AJ. Cytotoxic T-cell recognition of HIV proteins and peptides. AIDS. 1991;5:1049–1059. [PubMed] [Google Scholar]
  • 34.Torpey D, Huang XL, Armstrong J, Ho M, Whiteside T, McMahon D, et al. Effects of adoptive immunotherapy with autologous CD8+ T lymphocytes on immunological parameters: lymphocyte subsets and cytotoxic activity. Clin Immunol Immunopthol. 1993;68:263–272. doi: 10.1006/clin.1993.1127. [DOI] [PubMed] [Google Scholar]
  • 35.Miller MD, Lord CI, Stallard V, Mazzara GP, Letvin NL. The gagspecific cytotoxic T lymphocytes in rhesus monkeys infected with the simian immunodeficiency virus ofmacaques. J Immunol. 1990;144:122–128. [PubMed] [Google Scholar]
  • 36.Hahn BH, Shaw GM, Taylor ME, Redfield RR, Markham PD, Salahuddin SZ, et al. Genetic variation in HTLV-UIII/LAV over time in patients with AIDS or at risk for AIDS. Science. 1986;232:1548–1553. doi: 10.1126/science.3012778. [DOI] [PubMed] [Google Scholar]
  • 37.Saag MS, Hahn BH, Gibbons J, Li YX, Parks ES, Parks WP, et al. Extensive variation of HIV type-l invivo. Nature. 1988;334:440–444. doi: 10.1038/334440a0. [DOI] [PubMed] [Google Scholar]
  • 38.Lyerly HK, Matthews TJ, Langlois AJ, Bolognesi DP, Weinhold KJ. Human T-cell lymphotropic virus IIIB glycoprotein (gpl20) bound to CD4 determinants on normal lymphocytes and expressed by infected cells serves as target for immune attack. Proc Natl Acad Sci USA. 1987;84:4601–4605. doi: 10.1073/pnas.84.13.4601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Michel F, Hoffenbach A, Froussard P, Langlade-Demoyem P, Kaczorek M, Kieny MP, et al. HIV-1 env, nef, and gag-specific T-cell immunity in mice: conserved epitopes in Nef P27 and gag P25 proteins. AIDS Res Hum Retroviruses. 1992;8:469–478. doi: 10.1089/aid.1992.8.469. [DOI] [PubMed] [Google Scholar]
  • 40.Littaua RA, Oldstone MBA, Takeda A, Debouck C, Wong JT, Tuazon CU, et al. An HLA-C-restricted CD8+ cytotoxic T-lymphocyte clone recognizes a highly conserved epitope on human immunodeficiency virus type l gag. J Virol. 1991;65:4051–4056. doi: 10.1128/jvi.65.8.4051-4056.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Johnson P, Trocha A, Yang L, Mazzara GP, Panicali DL, Buchanan TM, et al. HIV-1 gag-specific cytotoxic T lymphocytes recognize multiple highly conserved epitopes. J Immunol. 1991;147:1512–1521. [PubMed] [Google Scholar]
  • 42.Buseyne F, McChesney M, Porrot F, Kovarik S, Guy B, Riviere Y. Gag-specific cytotoxic T lymphocytes from human immunodeficiency virus type 1-infected individuals: Gag epitopes are clustered in three regions of the p24 gag protein. J Virol. 1993;67:694–702. doi: 10.1128/jvi.67.2.694-702.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43.Koenig S, Fuerst TR, Wood LV, Woods RM, Suzich JA., Jones GM, et al. Mapping the fine specificity of a cytolytic T-cell response to HIV-1 nef protein. J Immunol. 1990;145:127–135. [PubMed] [Google Scholar]
  • 44.Hadida F, Parrot A, Kieny MP, Sadat-Sowti B, Mayaud C, Debre P, et al. Carboxyl-terminal and central regions of human immunodeficiency virus-1 NEF recognized by cytotoxic T lymphocytes from lymphoid organs. An in vitro limiting dilution analysis. J Clin Invest. 1992;89:53–60. doi: 10.1172/JCI115585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Walker BD, Flexner C, BirchLimberger K, Fisher L, Paradis TJ, Aldorini A, et al. Long-term culture and fine specificity of human cytotoxic T-lymphocyte clones reactive with HIV-1. Proc Natl Acad Sci USA. 1989;86:9514–9518. doi: 10.1073/pnas.86.23.9514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Walker BD, Flexner C, Paradis TJ, Fuller TC, Hirsch MS, Schooley RT, et al. HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals. Science. 1988;240:64–66. doi: 10.1126/science.2451288. [DOI] [PubMed] [Google Scholar]
  • 47.Salk J, Bretscher PA, Salk PL, Clerici M, Shearer G. A strategy for prophylactic vaccination against HIV. Science. 1993;260:1270–1278. doi: 10.1126/science.8098553. [DOI] [PubMed] [Google Scholar]
  • 48.Atlan H, Gersten MJ, Salk PL, Salk J. Can AIDS be prevented by Tcell vaccination? Immunol Today. 1993;14:200–202. doi: 10.1016/0167-5699(93)90162-E. [DOI] [PubMed] [Google Scholar]
  • 49.Clerici M, Shearer GM. A Th1→Th2 switch is a critical step in the etiology of HIV infection. ImmunolToday. 1993;14:107–111. doi: 10.1016/0167-5699(93)90208-3. [DOI] [PubMed] [Google Scholar]
  • 50.Parrish CR. The relationship between humoral and cellular immunity. Transplant Rev. 1972;13:35–66. doi: 10.1111/j.1600-065x.1972.tb00059.x. [DOI] [PubMed] [Google Scholar]
  • 51.Lucey DR, McGuire SA, Clerici M, Hall K, Benton J, Butzin CA, et al. Comparison of spinal fluid Β2-microglobulin levels with CD4+ T-cell count, in vitro T helper cell function, and spinal fluid IgG parameters in 163 neurologically normal adults infected with the HIV-1. J Infect Dis. 1991;163:971–975. doi: 10.1093/infdis/163.5.971. [DOI] [PubMed] [Google Scholar]
  • 52.Clerici M, Hakim FT, Venzon DJ, Blatt S, Hendrix CW, Wynn TA, et al. Changes in interleukin-2 and interleukin-4 production in asymptomatic, human immunodeficiency virus-seropositive individuals. J Clin Invest. 1993;91:759–765. doi: 10.1172/JCI116294. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Frankel FR, Hegde S, Lieberman J, Paterson Y. Induction of cell-mediated immune responses to human immunodeficiency virus type 1 Gag protein by usingListeria monocytogenes as a live vaccine vector. J Immunol. 1995;155:4775–4782. [PubMed] [Google Scholar]
  • 54.Paterson Y, Heber-Katz E. Antigen presentation of self-antigens. In: Bona CA, Siminovitch K, Theophilopoulos AN, Zanetti M, editors. The Molecular Pathology of Autoimmunity. Switzerland: Harwood Academic Publishers; 1993. pp. 83–99. [Google Scholar]
  • 55.Ota K, Matsui M, Milford EL, Mackin GA, Weiner HL, Hafler DA. T-cell recognition of an immunodominant myelin basic protein epitope in multiple sclerosis. Nature. 1990;346:183–187. doi: 10.1038/346183a0. [DOI] [PubMed] [Google Scholar]
  • 56.Allegretta M, Nicklaus JA, Sriram S, Albertini RJ. T-cells responsive to myelin basic protein in patients with MS. Science. 1990;147:718–721. doi: 10.1126/science.1689076. [DOI] [PubMed] [Google Scholar]
  • 57.Heber-Katz E, Acha-Orbea H. The V-region disease hypothesis: Evidence from autoimmune encephalomyelitis. Immunol Today. 1989;10:164–169. doi: 10.1016/0167-5699(89)90174-6. [DOI] [PubMed] [Google Scholar]
  • 58.Ben-Nun A, Wekerle H, Cohen I. Vaccination against autoimmune encephalomyelitis using attenuated cells of a T lymphocyte line reactive against myelin basic protein. Nature. 1981;292:60–62. doi: 10.1038/292060a0. [DOI] [PubMed] [Google Scholar]
  • 59.Owhashi M, Heber-Katz E. Protection from experimental allergic encephalomyelitis conferred by a monoclonal antibody directed against a shared idiotype on rat T-cell receptors specific for myelin basic protein. J Exp Med. 1989;168:2153–2164. doi: 10.1084/jem.168.6.2153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Hashim GA, Vandenbark AA, Galang AB, Diamanduros T, Carvalho E, Srinivasan J, et al. Antibodies specific for V beta 8 receptor peptide suppress experimental autoimmune encephalomyelitis. J Immunol. 1990;144:4621–4627. [PubMed] [Google Scholar]
  • 61.Matsumoto Y, Tsuchida M, Hanawa H, Abo T. Successful prevention and treatment of autoimmune encephalomyelitis by short-term administration of anti-T-cell receptor αΒ antibody. Immunology. 1994;81:1–7. [PMC free article] [PubMed] [Google Scholar]
  • 62.Howell MD, Winters ST, Olee T, Powell HC, Carlo DJ, Brostoff SW. Vaccination against experimental allergic encephalomyelitis with T-cell receptor peptides. Science. 1989;286:668–670. doi: 10.1126/science.2814489. [DOI] [PubMed] [Google Scholar]
  • 63.Vandenbark AA, Hashim G, Offner H. Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature. 1989;341:541–544. doi: 10.1038/341541a0. [DOI] [PubMed] [Google Scholar]
  • 64.Kumar V, Tabibiazar R, Geysen HM, Sercarz E. Immunodominant framework region 3 peptide from TCR VΒ8.2 chain controls murine experimental autoimmune encephalomyelitis. J Immunol. 1995;154:1941–1950. [PubMed] [Google Scholar]
  • 65.Weinberg AD, Celnik B, Vainiene M, Beunafe AC, Vandenbark AA, Offner H. The effect of TCR VΒ8 peptide protection and therapy on T-cell populations isolated from the spinal cords of lewis rats with experimental autoimmune encephalomyelitis. J Neuroimmunol. 1994;49:161–170. doi: 10.1016/0165-5728(94)90192-9. [DOI] [PubMed] [Google Scholar]
  • 66.Desquenne-Clark L, Esch TR, Otvos L, Heber-Katz E. T-cell receptor peptide immunization leads to enhanced and chronic experimental allergic encephalomyelitis. Proc Natl Acad Sci USA. 1991;88:7219–7223. doi: 10.1073/pnas.88.16.7219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Gaur A, Haspel R, Mayer JP, Fathman CG. Requirement for CD8+ cells in T-cell receptor peptideinduced clonal unresponsiveness. Science. 1993;259:91–94. doi: 10.1126/science.8418501. [DOI] [PubMed] [Google Scholar]
  • 68.Jiang H, Zhang S-L, Pernis B. Role of CD8+ T-cells in murine EAE. Science. 1992;256:1213–1215. doi: 10.1126/science.256.5060.1213. [DOI] [PubMed] [Google Scholar]
  • 69.Koh D-R, Fung-Leung W-P, Ho A, Gray D, Acha-Orbea H, Mak TW. Less mortality but more relapses in EAE in CD8-/-mice. Science. 1992;256:1210–1213. doi: 10.1126/science.256.5060.1210. [DOI] [PubMed] [Google Scholar]
  • 70.Kumar V, Sercarz EE. The involvement of T-cell receptor peptidespecific regulatory CD4+ T-cells in recovery from antigen-induced autoimmune disease. J Exp Med. 1993;178:909–916. doi: 10.1084/jem.178.3.909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71.Braciale TJ, Morrison LA, Sweetser MT, Sambrook J, Gething MJ, Braciale VL. Antigen presentation pathways to class I and class IIMHC-restricted T lymphocytes. Immunol Rev. 1987;98:95–114. doi: 10.1111/j.1600-065X.1987.tb00521.x. [DOI] [PubMed] [Google Scholar]
  • 72.Bennink JR, Yewdell JW. Recombinant vaccinia viruses as vectors for studying T-cell specificity and function. Curr Top Microbiol Immunol. 1990;163:153–184. doi: 10.1007/978-3-642-75605-4_6. [DOI] [PubMed] [Google Scholar]
  • 73.Mackett M, Smith GL, Moss B. Vaccinia virus: A selectable eukaryotic cloning and expression vector. Proc Natl Acad Sci USA. 1982;79:7415–7419. doi: 10.1073/pnas.79.23.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.Brown F, Schild GC, Ada GL. Recombinant vaccinia viruses as vaccines. Nature. 1986;319:549,550–549,550. doi: 10.1038/319549a0. [DOI] [PubMed] [Google Scholar]
  • 75.Chunduru S, Sutherland RM, Stewart G, Doms R, Paterson Y. Exploitation of VΒ8.2 T-cell receptor gene in amelioration of experimental allergic encephalomyelitis using a vaccinia virus vector. J Immunol. 1996;156:4940–4945. [PubMed] [Google Scholar]
  • 76.Vasquez NJ, Kane LP, Hedrick SM. Intracellular signals that mediate thymic negative selection. Immunity. 1994;1:45–56. doi: 10.1016/1074-7613(94)90008-6. [DOI] [PubMed] [Google Scholar]
  • 77.Cooper HM, Corradin GP, Paterson Y. The heme moiety of cytochrome c is an autoreactive Ir gene-restricted T-cell epitope. J Exp Med. 1988;168:1127–1143. doi: 10.1084/jem.168.3.1127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78.Sutherland RM, Pan Z-K, Caton AJ, Tang X, Cerasoli D, Paterson Y. Tcells from unprimed mice respond to the self antigen heme in a class II restricted manner at a frequency similar to alloresponses. Int Immunol. 1995;7:771–783. doi: 10.1093/intimm/7.5.771. [DOI] [PubMed] [Google Scholar]
  • 79.Sutherland RM, Brasseil S, Liu Q, Paterson Y. The self antigen heme evades immune recognition by sequestration in some hemoproteins. Eur J Immunol. 1995;25:1810–1814. doi: 10.1002/eji.1830250703. [DOI] [PubMed] [Google Scholar]
  • 80.Jenson AB, Rosenberg HS. Multiple viruses in diabetes mellitus. Prog Med Virol. 1984;29:197–217. [PubMed] [Google Scholar]
  • 81.Oldstone MBA. Molecular mimicry and autoimmune disease. Cell. 1987;50:819–820. doi: 10.1016/0092-8674(87)90507-1. [DOI] [PubMed] [Google Scholar]
  • 82.Hofman FM, von Hanwehr RI, Dinarello CA, Mizel SB, Hinton D, Merrill JE. Immunoregulatory molecules and IL 2 receptors identified in multiple sclerosis brain. J Immunol. 1986;136:1446–1453. [PubMed] [Google Scholar]
  • 83.Martin R, McFarland HF, McFarlin DE. Immunological aspects of demyelinating diseases. Ann Rev Immunol. 1992;10:153–187. doi: 10.1146/annurev.iy.10.040192.001101. [DOI] [PubMed] [Google Scholar]
  • 84.Woodroofe MN, Bellamy AS, Feldmann M, Davison AN, Cuzner MLJ. Immuno cytochemical characterization of the immune reaction in the central nervous system in multiple sclerosis. Neuroimmunology. 1986;74:135–352. doi: 10.1016/0022-510x(86)90100-0. [DOI] [PubMed] [Google Scholar]
  • 85.Johnson RT. The possible viral etiology of multiple sclerosis. Adv Neurol. 1975;13:1–46. [PubMed] [Google Scholar]
  • 86.Lavi E, Gilden DH, Wroblewska Z, Rorke LB, Weiss SR. Experimental demyelination produced by the A59 strain of mouse hepatitis virus. Neurology. 1984;34:597–603. doi: 10.1212/wnl.34.5.597. [DOI] [PubMed] [Google Scholar]
  • 87.Lampert PW, Sims JK, Kniazeff AJ. Mechanism of demyelination in JHM virus encephalomyelitis. Acta Neuropathol. 1973;24:76–85. doi: 10.1007/BF00691421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 88.Wang F, Stohlman SA, Fleming JO. Demyelination induced by murine hepatitis virus JHM strain (MHV-4) is immunologically mediated. J Neuroimmunol. 1990;30:31–41. doi: 10.1016/0165-5728(90)90050-W. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89.Fleming JO, Wang F, Trousdale MD, Hinton DR, Stohlman SA. Interaction of immune and central nervous systems: contribution of anti-viral Thyl+ ceils to demyelination induced by coronavirus JHM. Reg Immunol. 1993;5:37–43. [PubMed] [Google Scholar]
  • 90.Gombold JL, Sutherland RM, Lavi E, Paterson Y, Weiss SR. Mouse hepatitis virus A59-induced demyelination can occur in the absence of CD8+ T-cells. Microb Pathogen. 1995;18:211–221. doi: 10.1016/S0882-4010(95)90058-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.Sutherland RM, Chua M-M, Lavi E, Weiss SR, Paterson Y. CD4+ and CD8+ T-cells are not major effectors of mouse hepatitis virus A59-induced demyelination. Neuro Virol. 1997;3:225–228. doi: 10.3109/13550289709018297. [DOI] [PubMed] [Google Scholar]
  • 92.Williamson JO, Stohlman SA. Effective clearance of mouse hepatitis virus from the central nervous system requires both CD4+ and CD8+ Tcells. J Virol. 1990;64:4589–4592. doi: 10.1128/jvi.64.9.4589-4592.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 93.Pearce BD, Hobbs MV. McGraw TS MJ Buchmeier: Cytokine induction during T-cell mediated clearance of mouse hepatitis virus from neurons in vivo. J Virol. 1994;68:5483–5495. doi: 10.1128/jvi.68.9.5483-5495.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 94.Martin R, McFarland HF, McFarlin DE. Immunological aspects of demyelinating disease. Annu Rev Immunol. 1992;10:153–187. doi: 10.1146/annurev.iy.10.040192.001101. [DOI] [PubMed] [Google Scholar]
  • 95.Prineas JW, Connell F. The fine structure of chronically active multiple sclerosis plaques. Neurology. 1978;28:68–75. doi: 10.1212/wnl.28.9_part_2.68. [DOI] [PubMed] [Google Scholar]
  • 96.Traugott U. Characterization and distribution of lymphocyte populations in multiple scelerosis plaques versus autoimmune demyelinating lesions. Springer Semin Immunopathol. 1985;8:71–95. doi: 10.1007/BF00197248. [DOI] [PubMed] [Google Scholar]

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